Does Epidural Corticosteroid Application During Spinal Surgery Reduce Postoperative Pain?: An Adjunct to Multimodal Analgesia.

STUDY DESIGN: A prospective, randomized, placebo-controlled, double-blinded study. OBJECTIVE: To examine the effect of intraoperative epidural administration of Depo-Medrol on postoperative back pain and radiculitis symptoms in patients undergoing Transforaminal Lumbar Interbody Fusion (TLIF). SUMMARY OF BACKGROUND DATA: Postoperative pain is commonly experienced by patients undergoing spinal fusion surgery. Adequate management of intense pain is necessary to encourage early ambulation, increase patient satisfaction, and limit opioid consumption. Intraoperative steroid application has been shown to improve postoperative pain in patients undergoing lumbar decompression surgeries. There have been no studies examining the effect of epidural steroids on both back pain and radicular pain in patients undergoing TLIF. METHOD: In all, 151 patients underwent TLIF surgery using rh-BMP2 with 3 surgeons at a single institution. Of those, 116 remained in the study and were included in the final analysis. Based on a 1:1 randomization, a collagen sponge saturated with either Saline (1 cc) or Depo-Medrol (40 mg/1 cc) was placed at the annulotomy site on the TLIF level. Follow-up occurred on postoperative days 1, 2, 3, 7, and postoperative months 1, 2, and 3. Lumbar radiculopathy was measured by a modified symptom- and laterality-specific Visual Analog Scale (VAS) regarding the severity of back pain and common radiculopathy symptoms. RESULTS: The patients who received Depo-Medrol, compared with those who received saline, experienced significantly less back pain on postoperative days 1, 2, 3, and 7 (P<0.05). There was no significant difference in back pain beyond day 7. Radiculopathy-related symptoms such as leg pain, numbness, tingling, stiffness, and weakness tended to be reduced in the steroid group at most time points. CONCLUSION: This study provides Level 1 evidence that intraoperative application of Depo-Medrol during a TLIF surgery with rh-BMP2 significantly reduces back pain for the first week after TLIF surgery. The use of epidural Depo-Medrol may be a useful adjunct to multimodal analgesia for pain relief in the postoperative period.

Catastrophic acute failure of pelvic fixation in adult spinal deformity requiring revision surgery: a multicenter review of incidence, failure mechanisms, and risk factors.

OBJECTIVE: There are few prior reports of acute pelvic instrumentation failure in spinal deformity surgery. The objective of this study was to determine if a previously identified mechanism and rate of pelvic fixation failure were present across multiple institutions, and to determine risk factors for these types of failures. METHODS: Thirteen academic medical centers performed a retrospective review of 18 months of consecutive adult spinal fusions extending 3 or more levels, which included new pelvic screws at the time of surgery. Acute pelvic fixation failure was defined as occurring within 6 months of the index surgery and requiring surgical revision. RESULTS: Failure occurred in 37 (5%) of 779 cases and consisted of either slippage of the rods or displacement of the set screws from the screw tulip head (17 cases), screw shaft fracture (9 cases), screw loosening (9 cases), and/or resultant kyphotic fracture of the sacrum (6 cases). Revision strategies involved new pelvic fixation and/or multiple rod constructs. Six patients (16%) who underwent revision with fewer than 4 rods to the pelvis sustained a second acute failure, but no secondary failures occurred when at least 4 rods were used. In the univariate analysis, the magnitude of surgical correction was higher in the failure cohort (higher preoperative T1-pelvic angle [T1PA], presence of a 3-column osteotomy; p < 0.05). Uncorrected postoperative deformity increased failure risk (pelvic incidence-lumbar lordosis mismatch > 10°, higher postoperative T1PA; p < 0.05). Use of pelvic screws less than 8.5 mm in diameter also increased the likelihood of failure (p < 0.05). In the multivariate analysis, a larger preoperative global deformity as measured by T1PA was associated with failure, male patients were more likely to experience failure than female patients, and there was a strong association with implant manufacturer (p < 0.05). Anterior column support with an L5-S1 interbody fusion was protective against failure (p < 0.05). CONCLUSIONS: Acute catastrophic failures involved large-magnitude surgical corrections and likely resulted from high mechanical strain on the pelvic instrumentation. Patients with large corrections may benefit from anterior structural support placed at the most caudal motion segment and multiple rods connecting to more than 2 pelvic fixation points. If failure occurs, salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

Prospective comparison of dysphagia following anterior cervical discectomy and fusion (ACDF) with and without rhBMP-2.

BACKGROUND CONTEXT: Previous studies have called into question the safety of using rhBMP-2 in anterior cervical fusion due to the possibility of airway compromise and dysphagia. A retrospective chart review identified a significant increase in the severity of dysphagia after II-level ACDF with rhBMP-2 compared to patients who did not receive rhBMP-2. To date, this topic has not been studied prospectively. PURPOSE: Compare the incidence of dysphagia following anterior cervical discectomy and fusion (ACDF) when recombinant human bone morphogenetic protein-2 (rhBMP-2) is used with allograft compared to allograft alone. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: A total of 114 patients completed a baseline SWAL-QOL survey and met the inclusion criteria. Thirty-nine patients underwent I- or II-level ACDF with allograft plus 0.5mg rhBMP-2/level. 44 patients underwent ACDF with allograft alone. Thirty-one patients undergoing a lumbar decompression were enrolled in a third cohort to control for dysphagia secondary to intubation. OUTCOME MEASURES: The primary outcome measure was the 14-point SWAL-QOL dysphagia questionnaire. Other patient factors obtained from anesthesia and operative records were examined to evaluate their potential relationship to postoperative dysphagia. METHODS: The 14-point SWAL-QOL questionnaire was administered at multiple time points (pre-op, post-op 7 days, 6 weeks, 6 months, and at least 1 year). Multivariable repeated-measures analysis was applied to data. RESULTS: Baseline adjusted SWAL-QOL means 7 days after surgery were significantly different between the three study groups. These differences resolved by 6 weeks postoperative, beyond which point there were no differences. At final follow-up, baseline adjusted SWAL-QOL means at 1 year were similar for the three study groups. CONCLUSIONS: This single-center study of anterior cervical surgery demonstrated that the addition of rhBMP-2 to an ACDF increased postoperative dysphagia at 7 days after surgery, but these patients recover to levels comparable to those who underwent ACDF without rhBMP-2 or lumbar surgery within 6 weeks.

Is Timing to Surgery an Independent Risk Factor for Complications Following Operative Treatment of Periprosthetic Lower Extremity Fractures?

OBJECTIVE: To identify whether timing to surgery was related to major 30-day morbidity and mortality rates in periprosthetic hip and knee fractures [OTA/AO 3 (IV.3, V.3), OTA/AO 4 (V4)]. DESIGN: Retrospective database review. SETTING: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. PATIENTS: Patients in the NSQIP database with periprosthetic hip or knee fractures between 2007 and 2015. INTERVENTION: Surgical management of periprosthetic hip and knee fractures including revision or open reduction internal fixation. MAIN OUTCOME MEASUREMENTS: Major 30-day morbidity and mortality after operative treatment of periprosthetic hip or knee fractures. RESULTS: A total of 1265 patients, mean age 72, including 883 periprosthetic hip and 382 periprosthetic fractures about the knee were reviewed. Delay in surgery greater than 72 hours is a risk factor for increased 30-day morbidity in periprosthetic hip and knee fractures [relative risk = 2.90 (95% confidence interval: 1.74-4.71); P-value ≤ 0.001] and risk factor for increased 30-day mortality [relative risk = 8.98 (95% confidence interval: 2.14-37.74); P-value = 0.003]. CONCLUSIONS: Using NSQIP database to analyze periprosthetic hip and knee fractures, delay to surgery is an independent risk factor for increased 30-day major morbidity and mortality when controlling for patient functional status and comorbidities. Although patient optimization and surgical planning are paramount, minimizing extended delays to surgery is a potentially modifiable risk factor in the geriatric periprosthetic lower extremity fracture patient. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Relationship Between Cigarette Smoking and the Prevalence, Frequency and Severity of Back Pain.

The purpose of this study was to examine the relationship between smoking and back pain in a cross-sectional analysis. Using the Osteoarthritis Initiative database, a multi-center, longitudinal, observational cohort study with 4796 participants, we examined the prevalence of back pain and of limitations in activity due to back pain, as well as the frequency and severity of back pain in participants who were current smokers compared to those who had never smoked. Data was evaluated using binary and ordinal logistic regression analyses. An increase in prevalence, frequency and severity of back pain was strongly associated with smoking. This demonstrates a relationship between smoking and back pain; however, further studies are needed to evaluate causation. (Journal of Surgical Orthopaedic Advances 29(3):165-168, 2020).

Honey-Based Salve and Burdock Leaf Dressings as an Alternative to Surgical Debridement of a Traumatic Wound Eschar.

Objective: Nonviable necrotic eschar is an impedance to wound healing and can ultimately lead to failure of soft tissue coverage in traumatic or high-risk wounds. Topical therapeutic agents can provide a less invasive management alternative to surgical debridement of eschar. Approach: The case of a 40-year-old male with a traumatic right lower extremity amputation complicated by surgical incision ischemic eschar formation is reported. Honey-based salve with burdock leaf dressings was used to noninvasively manage eschar extending over the incision site. Images were obtained for 5 months of follow-up. Results: Five-month follow-up demonstrated complete resolution of eschar and re-epithelialization of skin in the affected region. Innovation: Honey-based salve with burdock leaf dressings shows promise for enhancing healing outcomes in traumatic wounds that develop nonviable eschar. Conclusion: Surgical debridement of an amputation stump with large ischemic eschar was avoided with the use of honey-based salve with burdock leaf dressings.

30-day Mortality Following Surgery for Spinal Epidural Abscess: Incidence, Risk Factors, Predictive Algorithm, and Associated Complications.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To determine incidence and timing of mortality following surgery for spinal epidural abscess (SEA), identify risk factors for mortality, and identify complications associated with mortality. SUMMARY OF BACKGROUND DATA: SEA is a serious condition with potentially devastating sequelae. There is a paucity of literature characterizing mortality following surgery for SEA. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used. Patients with a diagnosis of SEA were included. A Cox proportional hazards model identified independent risk factors for 30-day mortality. A predictive model for mortality was created. Multivariate models identified postoperative complications associated with mortality. RESULTS: There were 1094 patients included, with 40 cases of mortality (3.7%), the majority of which occurred within 2 weeks postoperatively (70%). Independent risk factors for 30-day mortality were age>60 years (hazard ratio [HR]: 2.147, P = 0.027), diabetes (HR: 2.242, P = 0.015), respiratory comorbidities (HR: 2.416, P = 0.037), renal comorbidities (HR: 2.556, P = 0.022), disseminated cancer (HR: 5.219, P = 0.001), and preoperative thrombocytopenia (HR: 3.276, P = 0.001). A predictive algorithm predicts a 0.3% mortality for zero risk factors up to 37.5% for 4 or more risk factors. A ROC area under curve (AUC) was 0.761, signifying a fair predictor (95% CI: 0.683-0.839, P < 0.001). Cardiac arrest (adjusted odds ratio [aOR]: 72.240, 95% confidence interval [CI]: 27.8-187.721, P < 0.001), septic shock (aOR: 15.382, 95% CI: 7.604-31.115, P < 0.001), and pneumonia (aOR: 2.84, 95% CI: 1.109-7.275, P = 0.03) were independently associated with mortality. CONCLUSION: The 30-day mortality rate following surgery for SEA was 3.7%. Of the mortalities that occurred within 30 days of surgery, the majority occurred within 2 weeks. Independent risk factors for mortality included older age, diabetes, hypertension, respiratory comorbidities, renal comorbidities, metastatic cancer, and thrombocytopenia. Risk for mortality ranged from 0.3% to 37.5% based on number of risk factors. Septic shock, cardiac arrest, and pneumonia were associated with mortality. LEVEL OF EVIDENCE: 3.

Assessing Foraminal Stenosis in the Cervical Spine: A Comparison of Three-Dimensional Computed Tomographic Surface Reconstruction to Two-Dimensional Modalities.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: The optimal radiographic modality for assessing cervical foraminal stenosis is unclear. Determination on conventional axial cuts is made difficult due in part to the complex, oblique orientation of the cervical neuroforamen. The utility of 3-dimensonal (3D) computed tomography (CT) reconstruction in improving neuroforaminal assessment is not well understood. The objective of this study is to determine inter-rater variability in grading cervical foraminal stenosis using 3 different CT imaging modalities: 3D CT surface reconstructions (3DSR), 2D sagittal oblique multiplanar reformations (2D-SOMPR), and conventional 2D axial CT imaging. METHODS: Pretreatment CT scans of 25 patients undergoing surgery for cervical spondylotic radiculopathy were analyzed at 2 levels: C5-C6 and C6-C7. Simple interrater agreement and kappa-Fleiss coefficients were calculated for each imaging modality and stenosis grade. Image reviewers (attending spine surgeon, attending neuroradiologist, spine fellow) interpreted each CT scan in 3 different formats: axial, 2D-SOMPR, and 3DSR. Four cervical foramina at 2 spinal levels were graded as normal (no stenosis), mild (≤25% stenosis), moderate (25%-50% stenosis), or severe (>50% stenosis). RESULTS: Across all imaging modalities, interrater reliability was fair when grading foraminal stenosis (κ < 0.4). Agreement was lowest for the axial images (κ = 0.119) and highest for the 3D CT reconstructions (κ = 0.334). 2D-SOMPR images also led to improved interrater reliability when compared with axial images (κ = 0.255). CONCLUSION: Grading cervical foraminal stenosis using conventional axial CT imaging is difficult with low interrater reliability. CT modalities that provide a circumferential view of the cervical foramen, such as 2D-SOMPR and 3D CT reconstruction, had higher rates of interobserver reliability in grading foraminal stenosis than conventional axial cuts, with 3D having the highest. As these 3D reconstructions can be obtained at no additional cost or radiation exposure over a conventional CT scan, and because they can provide useful information in determining levels being considered for surgical decompression, we recommend they be utilized when evaluating cervical foramina.

Surgical management of Gorham disease involving the upper cervical spine with occipito-cervical-thoracic fusion: a case report.

BACKGROUND CONTEXT: Gorham disease is a rare osteolytic condition, with only 17 reported cases primarily affecting the cervical spine. PURPOSE: We report the case of a 31-year-old woman with severe kyphotic instability and myelopathy of the upper cervical spine secondary to massive osteolysis of the posterior elements. The surgical management, clinical outcome, and review of the relevant literature are discussed. STUDY DESIGN: This is a case report and a literature review. PATIENT SAMPLE: This is a report of one patient with Gorham disease of the cervical spine. METHODS: We report the case of a 31-year-old woman with Gorham disease affecting the upper cervical spine. Combined posterior and anterior stabilization and fusion was performed from the occiput to the thoracic spine. RESULTS: Six-year follow-up with annual computed tomography imaging showed solid fusion from the occiput to T2. No spread or local recurrence has developed to date. CONCLUSIONS: Correction of severe instability with myelopathy due to Gorham disease of the upper cervical spine was achieved through posterior and anterior occipito-cervical-thoracic fusion.

Potent benzoazepinone γ-secretase modulators with improved bioavailability.

The triazolyl amide γ-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain Aß42 lowering maintained in both transgenic mouse and rat.

Lead(II) complex formation with L-cysteine in aqueous solution.

The lead(II) complexes formed with the multidentate chelator L-cysteine (H2Cys) in an alkaline aqueous solution were studied using (207)Pb, (13)C, and (1)H NMR, Pb LIII-edge X-ray absorption, and UV-vis spectroscopic techniques, complemented by electrospray ion mass spectrometry (ESI-MS). The H2Cys/Pb(II) mole ratios were varied from 2.1 to 10.0 for two sets of solutions with CPb(II) = 0.01 and 0.1 M, respectively, prepared at pH values (9.1-10.4) for which precipitates of lead(II) cysteine dissolved. At low H2Cys/Pb(II) mole ratios (2.1-3.0), a mixture of the dithiolate [Pb(S,N-Cys)2](2-) and [Pb(S,N,O-Cys)(S-HCys)](-) complexes with average Pb-(N/O) and Pb-S distances of 2.42 ± 0.04 and 2.64 ± 0.04 Å, respectively, was found to dominate. At high concentration of free cysteinate (>0.7 M), a significant amount converts to the trithiolate [Pb(S,N-Cys)(S-HCys)2](2-), including a minor amount of a PbS3-coordinated [Pb(S-HCys)3](-) complex. The coordination mode was evaluated by fitting linear combinations of EXAFS oscillations to the experimental spectra and by examining the (207)Pb NMR signals in the chemical shift range δPb = 2006-2507 ppm, which became increasingly deshielded with increasing free cysteinate concentration. One-pulse magic-angle-spinning (MAS) (207)Pb NMR spectra of crystalline Pb(aet)2 (Haet = 2-aminoethanethiol or cysteamine) with PbS2N2 coordination were measured for comparison (δiso = 2105 ppm). The UV-vis spectra displayed absorption maxima at 298-300 nm (S(-) → Pb(II) charge transfer) for the dithiolate PbS2N(N/O) species; with increasing ligand excess, a shoulder appeared at ∼330 nm for the trithiolate PbS3N and PbS3 (minor) complexes. The results provide spectroscopic fingerprints for structural models for lead(II) coordination modes to proteins and enzymes.

Lead(II) binding to the chelating agent D-penicillamine in aqueous solution.

A spectroscopic investigation of the complexes formed between the Pb(II) ion and D-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet-visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S(-) → Pb(II) ligand-to-metal charge-transfer. The downfield (13)C NMR chemical shift for the penicillamine COO(-) group confirmed Pb(II) coordination. The (207)Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state (207)Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb-S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ((207)Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a Pb(II)S2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)](2-n) (n = 0-1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.

Redetermination of (d-penicillaminato)lead(II).

In the title coordination polymer, [Pb(C(5)H(9)NO(2)S)](n) {systematic name: catena-poly[(µ-2-amino-3-methyl-3-sulfido-butano-ato)lead(II)]}, the d-penicillaminate ligand coordin-ates to the metal ion in an N,S,O-tridentate mode. The S atom acts as a bridge to two neighbouring Pb(II) ions, thereby forming a double thiol-ate chain. Moreover, the coordinating carboxyl-ate O atom forms bridges to the Pb(II) ions in the adjacent chain. The overall coordination sphere of the Pb(II) ion can be described as a highly distorted penta-gonal bipyramid with a void in the equatorial plane between the long Pb-S bonds probably occupied by the stereochemically active inert electron pair. The amino H atoms form N-H⋯S and N-H⋯O hydrogen bonds, resulting in a cluster of four complex units, giving rise to an R(4) (4)(16) ring lying in the ab plane. The crystal structure of the title compound has been reported previously [Freeman et al. (1974 ▶). Chem. Soc. Chem. Commun. pp. 366-367] but the atomic coordinates have not been deposited in the Cambridge Structural Database (refcode DPENPB). Additional details of the hydrogen bonding are presented here.

Triazoles as γ-secretase modulators.

Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of γ-secretase activity, excellent pharmacokinetics and good central lowering of Aß42 in Sprague-Dawley rats.